MALDI tissue imaging, when enabled by Nanoparticulate (NP) Matrix implantation, is maturing into a useful preclinical tool for biomarker and drug discovery in our laboratory and at NIDA-IRP. Quantitatively reproducible images from serial coronal sections suggest that relative quantitation is now possible in rodent models of disease and injury. Nanoparticulate (NP) matrix implantation allows numerical quantitation of differences in biomarker levels in rodent disease and injury models. No commercial instrument which performs mass spectral molecular imaging of tissues has software capable of analyzing and displaying these quality data sets. 1) Software and hardware developed under our antecedent phase II for analyzing the multidimensional data from our MALDI-Ion Mobility-MS imaging system will be expanded to serve this need and will also have dual use in correlating molecular image quality with the nano-scale characterization of the NP matrices by advance materials analysis techniques such as the subnanometer resolution Zeiss Orion Helium Ion Microscope. 2) The continued growth of unique core shell NP matrices will continue to be aided by advanced materials analysis measurement of the NP structures and particle size distributions after implantation into the tissue. 3) Protocols for standards incorporation into and onto the tissue surface will attempt to prove the capability of relative and absolute quantitation in MALDI-MS imaging.